The purpose of this Revision to our UM1 Cooperative Agreement is to enhance the NCI-supported early development of experimental cancer therapeutics by merging the Phase 2 clinical trials program with the Experimental Therapeutics Clinical Trials Network (ETCTN) that is currently focused on Phase 1 clinical trials. The California Cancer Consortium (CCC) consists of the City of Hope Comprehensive Cancer Center (COH, the Lead Academic Organization, [LAO]), the University of California, Davis Cancer Center (UCD, Affiliated Organization [AO]), and the University of Southern California (USC)/Norris Comprehensive Cancer Center (USC, AO) and will add Stanford University Cancer Center (AO) with this Revision to our UM1. The CCC will integrate our extensive Phase 2 clinical trials program (currently funded through an NCI contract, N01) into a single administrative structure participating in the ETCTN. Our multidisciplinary group of investigators will contribute to ETCTN agent-specific trans-network drug development Project Teams from the combined expertise of COH, UCD, USC, and SU in the areas of molecular pharmacology, pharmacokinetics, pharmacodynamics, pharmacogenomics, signal transduction, cell cycle regulation, non-invasive imaging, and bioinformatics to conduct innovative, laboratory-directed early phase developmental and pharmacokinetic studies. We propose to utilize the combined patient and scientific resources and expertise of UCD, COH, USC, and SU to accomplish the following Specific Aims: (Aim 1) to rapidly design, initiate and complete laboratory-driven Phase 2 clinical trials evaluating the safety and efficacy of NCI-sponsored agents, alone or in combination, in order to maximize the patient, scientific, and mentorship/career development resources of an established Consortium with demonstrated expertise in clinical drug development; (Aim 2) to employ a systematic approach to collection, processing, and storage of blood, normal and tumor tissue, and other relevant biologic samples for molecular and pharmacologic studies in the context of Phase 2 oncology trials; and (Aim 3) to develop scientific rationale for proposed trials using advanced preclinical models; to evaluate biologic effects of novel therapeutics (including immunotherapy) on their molecular or biologic targets; to incorporate appropriate study designs, imaging, and statistical methods for assessment of intermediate endpoints; and to correlate findings with clinically relevant outcomes in the Phase 2 setting. A single Data Coordinating Center located at the LAO currently manages participation (clinical trial management, patient accrual, and communication with multiple NCI components and staff) by the LAO and all CCC AOs for both NCI-Sponsored Phase 1 trials (under the current UM1) and Phase 2 trials (under the current N01 contract), which will make the incorporation of the current CCC Phase 2 program into the ETCTN structure seamless.